scholarly journals Enzyme modification using mutation site prediction method for enhancing the regioselectivity of substrate reaction sites

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jinzen Ikebe ◽  
Munenori Suzuki ◽  
Aya Komori ◽  
Kaito Kobayashi ◽  
Tomoshi Kameda
Keyword(s):  
Cytochrome P450 ◽  
Adverse Effects ◽  
Prediction Method ◽  
Raw Material ◽  
Target Product ◽  
Mutation Site ◽  
Enzyme Modification ◽  
Site Prediction ◽  
Multiple Products ◽  
Ranked List

AbstractEnzymes with low regioselectivity of substrate reaction sites may produce multiple products from a single substrate. When a target product is produced industrially using these enzymes, the production of non-target products (byproducts) causes adverse effects such as increased processing costs for purification and the amount of raw material. Thus it is required the development of modified enzymes to reduce the amount of byproducts’ production. In this paper, we report a method called mutation site prediction for enhancing the regioselectivity of substrate reaction sites (MSPER). MSPER takes conformational data for docking poses of an enzyme and a substrate as input and automatically generates a ranked list of mutation sites to destabilize docking poses for byproducts while maintaining those for target products in silico. We applied MSPER to the enzyme cytochrome P450 CYP102A1 (BM3) and the two substrates to enhance the regioselectivity for four target products with different reaction sites. The 13 of the total 14 top-ranked mutation sites predicted by MSPER for the four target products succeeded in selectively enhancing the regioselectivity up to 6.4-fold. The results indicate that MSPER can distinguish differences of substrate structures and the reaction sites, and can accurately predict mutation sites to enhance regioselectivity without selection by directed evolution screening.

Processed Gingers: Current and Prospective Use in Food, Cosmetic, and Pharmaceutical Industry

2019 ◽  
Vol 10 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Jae-Suk Choi
Keyword(s):  
Pharmaceutical Industry ◽  
Adverse Effects ◽  
Shelf Life ◽  
Traditional Medicine ◽  
Functional Foods ◽  
Zingiber Officinale ◽  
Raw Material

Ginger (Zingiber officinale) has been widely used in traditional medicine, and as raw material for cosmetics, beverages, and health functional foods. However, some adverse effects of ginger have been reported. In addition, the hot and pungent taste of ginger leads to reduced consumption. To overcome these problems, methods for the production of fermented, steamed (or steamed-dried), aged, roasted and beopje ginger have been developed. This review provides an overview and summary of new ginger processing procedures, including methods to reduce the pungent flavor of ginger, extend shelf-life, increase the health-functional compound content, and improve safety. These attempts might improve the consumption of ginger as well as prospective applications of processed ginger for food, cosmetics, and the pharmaceutical industry, also as discussed in various patents.

scholarly journals Forecast of International Trade of Lithium Carbonate Products in Importing Countries and Small-Scale Exporting Countries

2021 ◽  
Vol 13 (3) ◽  
pp. 1251
Author(s):  
Yichi Zhang ◽  
Zhiliang Dong ◽  
Sen Liu ◽  
Peixiang Jiang ◽  
Cuizhi Zhang ◽  
...  
Keyword(s):  
International Trade ◽  
Large Scale ◽  
Prediction Method ◽  
Lithium Ion ◽  
Lithium Carbonate ◽  
Raw Material ◽  
Small Scale ◽  
Trade Restrictions ◽  
Energy Field ◽  
Structure Of Trade

As the raw material of lithium-ion batteries, lithium carbonate plays an important role in the development of new energy field. Due to the extremely uneven distribution of lithium resources in the world, the security of supply in countries with less say would be greatly threatened if trade restrictions or other accidents occurred in large-scale exporting countries. It is of great significance to help these countries find new partners based on the existing trade topology. This study uses the link prediction method, based on the perspective of the topological structure of trade networks in various countries and trade rules, and eliminates the influence of large-scale lithium carbonate exporting countries on the lithium carbonate trade of other countries, to find potential lithium carbonate trade links among importing and small-scale exporting countries, and summarizes three trade rules: (1) in potential relationships involving two net importers, a relationship involving either China or the Netherlands is more likely to occur; (2) for all potential relationships, a relationship that actually occurred for more than two years in the period in 2009–2018 is more likely to occur in the future; and (3) potential relationships pairing a net exporter with a net importer are more likely to occur than other country combinations. The results show that over the next five to six years, Denmark and Italy, Netherlands and South Africa, Turkey and USA are most likely to have a lithium carbonate trading relationship, while Slovenia and USA, and Belgium and Thailand are the least likely to trade lithium carbonate. Through this study, we can strengthen the supply security of lithium carbonate resources in international trade, and provide international trade policy recommendations for the governments of importing countries and small-scale exporting countries.

scholarly journals Restarting antidepressant and antipsychotic medication after intentional overdoses: need for evidence-based guidance

2019 ◽  
Vol 9 ◽  
pp. 204512531983688
Author(s):  
Emma Tay ◽  
Andreas Sotiriou ◽  
Garry G. Graham ◽  
Kay Wilhelm ◽  
Leone Snowden ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Adverse Effects ◽  
Antipsychotic Drugs ◽  
Plasma Concentrations ◽  
Pharmacokinetic Data ◽  
Psychoactive Drugs ◽  
Cytochrome P450 Enzymes ◽  
Psychoactive Medication ◽  
Drug Overdoses ◽  
P450 Inhibitors

Intentional drug overdoses with antidepressant and antipsychotic medications are an increasingly common problem. Currently, there is little guidance with regard to reintroduction of these medications after intentional overdoses. We have used published toxicological and pharmacokinetic data to obtain factors which control the recovery from overdoses. From such data, we have proposed guidance regarding their reintroduction, provided there are no adverse effects or contraindications. Tentatively, we suggest that when adverse effects from the overdose are lost, treatment could recommence after a further mean half-life of elimination. Most antidepressant and antipsychotic drugs are metabolized by cytochrome P450 enzymes and, where cytochrome P450 inhibitors are co-ingested, serial plasma concentrations should optimally be obtained in order to assess a suitable time for reintroduction of the psychoactive drugs. We hope the proposals presented will stimulate research and discussion that lead to better guidance for clinicians concerning reintroduction of psychoactive medication after intentional overdose.

scholarly journals Drug interactions with statins

2013 ◽  
Vol 63 (3) ◽  
pp. 277-293 ◽  
Author(s):  
Anida Causevic-Ramosevac ◽  
Sabina Semiz
Keyword(s):  
Cytochrome P450 ◽  
Adverse Effects ◽  
Drug Interactions ◽  
Liver Enzymes ◽  
Drug Transporters ◽  
Multiple Drug ◽  
Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitors ◽  
Coa Reductase ◽  
Asymptomatic Elevation

AbstractThe 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are generally well tolerated as monotherapy. Statins are associated with two important adverse effects, asymptomatic elevation in liver enzymes and myopathy. Myopathy is most likely to occur when statins are administered with other drugs. Statins are substrates of multiple drug transporters (including OAT- -P1B1, BCRP and MDR1) and several cytochrome P450 (CYP) enzymes (including CYP3A4, CYP2C8, CYP2C19, and CYP2C9). Possible adverse effects of statins can occur due to interactions in concomitant use of drugs that substantially inhibit or induce their methabolic pathway. This review summarizes the most important interactions of statins.

Characterization of Multiple Products of Cytochrome P450 2A6-Catalyzed Cotinine Metabolism

1999 ◽  
Vol 12 (7) ◽  
pp. 639-645 ◽  
Author(s):  
Sharon E. Murphy ◽  
Lisa M. Johnson ◽  
Dominic A. Pullo
Keyword(s):  
Cytochrome P450 ◽  
Multiple Products ◽  
Cytochrome P450 2A6

scholarly journals The use of metallurgical slag as a by-product of the steel industry in chemical melioration of acid soils

2014 ◽  
Vol 20 (3) ◽  
pp. 191-198 ◽  
Author(s):  
Aleksandra Stanojković-Sebić ◽  
Srboljub Maksimović ◽  
Dragana Jošić ◽  
Radmila Pivić
Keyword(s):  
Chemical Composition ◽  
Adverse Effects ◽  
Steel Industry ◽  
Chemical Properties ◽  
Acid Soils ◽  
Metallurgical Slag ◽  
Raw Material ◽  
Agricultural Practice ◽  
Controlled Conditions ◽  
Secondary Raw Material

The effect of metallurgical slag application on chemical properties of the soils with limited productive ability (Stagnosol), as well as on chemical composition of cultivated vegetables (spinach and cabbage) as experimental crops, through the vegetative experiments performed in semi-controlled conditions, was studied. The longterm investigations were aimed to define the main parameters for possible wider usage of this secondary raw material (by-product of the steel industry, respectively) for chemical melioration and fertilization of acid soils in Serbia, as well as to indicate the justification of its application in agricultural practice. Generally, it was concluded that the studied metallurgical slag of the standardized chemical composition can be added to the acid soils toward amelioration the fertility without adverse effects. 

scholarly journals An in vitro toolbox to accelerate anti-malarial drug discovery and development

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Susan A. Charman ◽  
Alice Andreu ◽  
Helena Barker ◽  
Scott Blundell ◽  
Anna Campbell ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Intrinsic Clearance ◽  
Target Product ◽  
Experimental Conditions ◽  
Data Set ◽  
Vitro Data ◽  
In Vitro Data

Abstract Background Modelling and simulation are being increasingly utilized to support the discovery and development of new anti-malarial drugs. These approaches require reliable in vitro data for physicochemical properties, permeability, binding, intrinsic clearance and cytochrome P450 inhibition. This work was conducted to generate an in vitro data toolbox using standardized methods for a set of 45 anti-malarial drugs and to assess changes in physicochemical properties in relation to changing target product and candidate profiles. Methods Ionization constants were determined by potentiometric titration and partition coefficients were measured using a shake-flask method. Solubility was assessed in biorelevant media and permeability coefficients and efflux ratios were determined using Caco-2 cell monolayers. Binding to plasma and media proteins was measured using either ultracentrifugation or rapid equilibrium dialysis. Metabolic stability and cytochrome P450 inhibition were assessed using human liver microsomes. Sample analysis was conducted by LC–MS/MS. Results Both solubility and fraction unbound decreased, and permeability and unbound intrinsic clearance increased, with increasing Log D7.4. In general, development compounds were somewhat more lipophilic than legacy drugs. For many compounds, permeability and protein binding were challenging to assess and both required the use of experimental conditions that minimized the impact of non-specific binding. Intrinsic clearance in human liver microsomes was varied across the data set and several compounds exhibited no measurable substrate loss under the conditions used. Inhibition of cytochrome P450 enzymes was minimal for most compounds. Conclusions This is the first data set to describe in vitro properties for 45 legacy and development anti-malarial drugs. The studies identified several practical methodological issues common to many of the more lipophilic compounds and highlighted areas which require more work to customize experimental conditions for compounds being designed to meet the new target product profiles. The dataset will be a valuable tool for malaria researchers aiming to develop PBPK models for the prediction of human PK properties and/or drug–drug interactions. Furthermore, generation of this comprehensive data set within a single laboratory allows direct comparison of properties across a large dataset and evaluation of changing property trends that have occurred over time with changing target product and candidate profiles.

The Purification and Analysis of 6 - Hydroxy -2 - Naphthoic Acid

2012 ◽  
Vol 602-604 ◽  
pp. 1391-1395
Author(s):  
Yuan Jun Song ◽  
Chun Zhang ◽  
Jing Jing Li
Keyword(s):  
Melting Point ◽  
High Performance ◽  
High Performance Liquid Chromatographic ◽  
Point Method ◽  
Raw Material ◽  
Target Product ◽  
Ultraviolet Spectrophotometry ◽  
Standard Samples ◽  
Naphthoic Acid ◽  
Liquid Chromatographic

When synthetizing 2 - hydroxy - 6 - naphthoic acid with 2 - naphthol as raw material , we use a variety of methods to characterize and analyze the intermediates and target product . Through melting point method, the melting point of HNA we synthetized is showed to be slightly lower than standard samples. High performance liquid chromatographic shows that the purity of 2 - methoxy - 6 - naphthoic acid 2 - hydroxy - 6 - naphthoic acid reach up to 81.98% and 99.0% respectively. The purity of 2-hydroxyl-6-naphthoic acid is showed to be 97.1% with ultraviolet spectrophotometry.

scholarly journals Expression of Genes Related to Carrageenan Synthesis during Carposporogenesis of the Red Seaweed Grateloupia imbricata

Marine Drugs ◽  
2020 ◽  
Vol 18 (9) ◽  
pp. 432
Author(s):  
Pilar Garcia-Jimenez ◽  
Sara R. Mantesa ◽  
Rafael R. Robaina
Keyword(s):  
Cytochrome P450 ◽  
Stress Proteins ◽  
Life Cycles ◽  
Raw Material ◽  
Red Seaweed ◽  
Red Seaweeds ◽  
Temporal Regulation ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Two Stages

Carrageenan, the foremost constituent of extracellular matrix of some rhodophyta, is a galactan backbone with a different number of sulphate groups attached. Variations of degree of sulphation are associated with different types of carrageenans, which vary according to seaweed life cycles, and have consequences for the exploitation of this raw material. In this work, we used three well-recognised stages of development thalli and two stages of cystocarp maturation to analyse genes that encode addition and elimination of sulphate groups to cell-wall galactan of the red seaweed Grateloupia imbricata. Expressions of carbohydrate sulfotransferase and galactose-6 sulfurylase and genes encoding stress proteins such as cytochrome P450 and WD40, were examined. Results showed that transcript expression of carbohydrate sulfotransferase occurs at all stage of thalli development. Meanwhile galactose-6 sulfurylase expressions displayed different roles, which could be related to a temporal regulation of cystocarp maturation. Cytochrome P450 and WD40 are related to the disclosure and maturation of cystocarps of G. imbricata. Our conclusion is that differential expression of genes encoding proteins involved in the sulphation and desulphation of galactan backbone is associated with alterations in thalli development and cystocarp maturation in the red seaweed Grateloupia imbricata. Exploitation of industry-valued carrageenan will depend on insight into gene mechanisms of red seaweeds.

Sign in / Sign up

Export Citation Format

Share Document